The proposed research will study the pathogenesis of pancreatic and extrapancreatic lesions encountered in a contagious model of diabetes mellitus afforded by a colony of guinea pigs. This light and electron microscopic study of disease-related, as opposed to age-related, changes in the kidneys, eyes, nervous system as well as pancreatic islets, will be correlated with the clinical characteristics of the animals. The major emphasis for the forthcoming grant period will be the definition of the cytologic and histologic progression of these lesions in chronic overt diabetes mellitus. In addition, we will attempt to define asymptomatic diabetes mellitus, as well as the prediabetic state, in the guinea pig model. Where possible, these changes will be correlated with the pathology seen in altered states of endocrine metabolism in man concentrating on the islet pathology in human diabetes mellitus. Techniques to be used for this predominantly pathologic study will consist of the techniques of light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) and where appropriate, elemental analysis using an energy dispersive X-ray analyzer (EDAX 707).